Association of Fibroblast Growth Factor-23 Levels and Angiotensin-Converting Enzyme Inhibition in Chronic Systolic Heart Failure

JACC Heart Fail. 2015 Oct;3(10):829-39. doi: 10.1016/j.jchf.2015.05.012.

Abstract

Objectives: The aim of this study was to evaluate the association of fibroblast growth factor (FGF)-23 with clinical and laboratory findings, the prognostic value of FGF-23, and the relationship between angiotensin-converting enzyme inhibitor (ACEi) therapy, FGF-23 levels, and outcomes in patients with chronic systolic heart failure (HF).

Background: FGF-23 is a bone-derived hormone regulating mineral metabolism. Higher FGF-23 levels are associated with an increased risk of cardiovascular mortality or HF development. Mechanisms leading to increased FGF-23 and its prognostic value have not been thoroughly studied in HF.

Methods: FGF-23 was measured in 369 patients (mean age 59 ± 11 years, 84% male) with systolic HF. Patients were followed for adverse events (e.g., death, urgent heart transplantation, ventricular assist device implantation).

Results: Tricuspid regurgitation severity, chronic kidney disease (CKD), alkaline phosphatase concentrations, inferior vena cava dilation, and absence of ACEi therapy were independently associated with FGF-23. FGF-23 was independently associated with outcomes in patients without CKD (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.14 to 1.78), but not in CKD patients (HR: 1.12, 95% CI: 0.87 to 1.45). In patients without CKD and with FGF-23 in the highest tertile, ACEi therapy was associated with a lower risk of adverse events (HR: 0.42, 95% CI: 0.21 to 0.81), whereas no association was seen in the remaining patients (HR: 1.18, 95% CI: 0.52 to 2.70).

Conclusions: In systolic HF, elevated FGF-23 is an independent predictor of adverse events, particularly in patients with preserved renal function. The association of FGF-23 with adverse events likely reflects early alterations of renal hemodynamics and renin-angiotensin system activation. Increased FGF-23 may identify a subset of HF patients benefiting from ACEi therapy.

Keywords: adverse events; angiotensin-converting enzyme inhibitor; fibroblast growth factor-23; heart failure; outcome.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon / methods
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers
  • Chronic Disease
  • Cohort Studies
  • Echocardiography, Doppler
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Heart Failure, Systolic / blood*
  • Heart Failure, Systolic / complications
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / physiopathology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • FGF23 protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23